NM_001318895.3:c.739G>C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001318895.3(FHL2):āc.739G>Cā(p.Asp247His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
FHL2
NM_001318895.3 missense
NM_001318895.3 missense
Scores
1
14
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.12
Genes affected
FHL2 (HGNC:3703): (four and a half LIM domains 2) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. This protein is thought to have a role in the assembly of extracellular membranes. Also, this gene is down-regulated during transformation of normal myoblasts to rhabdomyosarcoma cells and the encoded protein may function as a link between presenilin-2 and an intracellular signaling pathway. Multiple alternatively spliced variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249856Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135198
GnomAD3 exomes
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249856
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135198
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727166
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31
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727166
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D;D;D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;.;.;.;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;M;M;M;M;M
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
.;D;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.12
.;.;B;B;B;B;B
Vest4
MutPred
0.46
.;.;Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);Gain of methylation at K252 (P = 0.1134);
MVP
ClinPred
D
GERP RS
Varity_R
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at